Current Position
Vice Professor
The 2 nd Xiangya hospital, Central-South University
Research Forum Session

Topic: Activation of EphrinB2 signaling promotes adaptive venous remodeling in murine arteriovenous fistulae


Objective: Arteriovenous fistulae (AVF) are the preferred mode of vascular access for hemodialysis. Prior to use, AVF remodel by thickening and dilating to achieve a functional conduit, via an adaptive process characterized by expression of molecular markers characteristic of both venous and arterial identity. Although signaling via EphB4, a determinant of venous identity, mediates AVF maturation, the role of its counterpart EphrinB2, a determinant of arterial identity, remains unclear. We hypothesize that EphrinB2 signaling is active during AVF maturation and may be a mechanism of venous remodeling.
Results: Venous remodeling during AVF maturation was characterized by increased expression of EphrinB2 as well as Akt1, extracellular signal-regulated kinases 1/2 (ERK1/2), and p38. Activation of EphrinB2 with EphB4-Fc increased phosphorylation of EphrinB2, endothelial nitric oxide synthase (eNOS), Akt1, ERK1/2 and p38 and was associated with increased diameter and wall thickness in the AVF. Both mouse and human endothelial cells treated with EphB4-Fc increased phosphorylation of EphrinB2, eNOS, Akt1, ERK1/2 and p38, and increased endothelial cell tube formation and migration.
Conclusions: Activation of EphrinB2 signaling by EphB4-Fc was associated with adaptive venous remodeling in vivo, while activating endothelial cell function in vitro. Regulation of EphrinB2 signaling may be a new strategy to improve AVF maturation and patency.